Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess anti-insomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmaco-metabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine N-methyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Chronic refractory wounds have been a challenge for clinical treatment because of their diverse causative factors and complex pathological processes, long healing times, and high treatment costs. The microenvironment of the wound surface includes the external microenvironment of the periwound surface, the internal microenvironment of the wound surface, and subsurface physiological structures. Research on clinical treatment strategies based on the microenvironment of chronic refractory wounds continues to innovate and make progress. Hydrogels have the advantages of high-water content, adjustable performance, good biocompatibility, and similarity to extracellular matrix. The ability of hydrogels to load drugs and their modification to confer excellent tissue adhesion, antibacterial, antioxidant, and modulation of inflammatory factor expression can be used to achieve a multi-factor response and modulation of the physical, chemical, and biological aspects of the trauma microenvironment. Therefore, hydrogels have outstanding advantages and clinical application prospects in the repair of chronic, difficult-to-heal wounds. In this review paper, the characteristics and etiology of chronic refractory wounds were introduced, and the classification of microenvironment-responsive hydrogels for chronic refractory wounds and their application in the repair of refractory wounds were reviewed. Besides, the shortcomings of current hydrogels were discussed, and an outlook was proposed.

Objective To investigate the value of cytokines in bile combined with clinical indices in predicting the degree of liver injury after liver transplantation. MethodsA total of 16 patients undergoing liver transplantation who were hospitalized in Center of Organ Transplantation, The Affiliated Hospital of Qingdao University, from January to December 2018 were enrolled, and according to the level of alanine aminotransferase (ALT) on day 1 after surgery, the patients were divided into mild liver injury (ALT ＜500 U/L) group with 10 patients and severe liver injury (ALT ＞500 U/L) group with 6 patients. Bile samples were collected on days 1, 3, 5, and 7 after surgery, and MILLIPLEX assay was used to measure the levels of 17 cytokines. R software was used to perform principal component analysis (PCA) of bile cytokines and clinical indices and gene ontology (GO) enrichment analysis of bile cytokines. The two-independent-samples t-test was used for comparison of normally distributed continuous data between two groups; The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. A Spearman correlation analysis was performed to evaluate the correlation between clinical indices and bile cytokines. ROC curve analysis was used to evaluate the predictive value of cytokines in bile and clinical indices for liver injury after liver transplantation. ResultsCompared with the mild liver injury group, the severe liver injury group had significantly higher expression levels of bile Fractalkine (Z=-2.828, P=0.003), soluble CD40 ligand (sCD40L) (Z=-2.850, P=0.008), interleukin-4 (Z=-2.398, P=0.017), CXCL10 (Z=-2.475, P=0.023), and macrophage inflammatory protein-1α (Z=-1844, P=0.043). The correlation analysis showed that on day 1 after liver transplantation, aspartate aminotransferase, ALT, and lactate dehydrogenase were positively correlated with the levels of several cytokines in bile (all P＜0.05). The area under the ROC curve of Fractalkine, sCD40L and AST were 0.933 (0.812-1.000), 0.833 (0.589-1.000) and 0.917 (0.779-1.000), respectively, suggesting that AST and Fractalkine and sCD40L in bile on the first day after liver transplantation have significant predictive value for liver injury. The results of PCA showed that bile cytokines combined with clinical indices on day 1 after liver transplantation could better distinguish the patients with mild liver injury from those with severe liver injury. GO analysis showed that bile cytokines were associated with positive feedback regulation of external stimulus, cell chemotaxis, receptor ligand activity, cytokine activity, and cytokine-cytokine receptor interaction. ConclusionFractalkine and sCD40L in bile can predict the degree of liver injury after liver transplantation.

Objective: To quantitatively assess biochemical alterations in the cartilage of the subtalar and midtarsal joints in chronic lateral ankle instability (CLAI) patients with isolated anterior talofibular ligament (ATFL) injuries and combined calcaneofibular ligament (CFL) injuries using MRI T2 mapping. Materials and Methods: This study was performed according to regulations of the Committee for Human Research at our institution, and written informed consent was obtained from all participants. Forty CLAI patients (26 with isolated ATFL injuries and 14 with combined ATFL and CFL injuries) and 25 healthy subjects were recruited for this study. All participants underwent MRI scans with T2 mapping. Patients were assessed with the American Orthopedic Foot and Ankle Society (AOFAS) rating system. The subtalar and midtarsal joints were segmented into 14 cartilage subregions. The T2 value of each subregion was measured from T2 mapping images. Data were analyzed with ANOVA, the Student’s t test, and Pearson’s correlation coefficient. Results: T2 values of most subregions of the subtalar joint and the calcaneal facet of the calcaneocuboid joint in CLAI patients with combined CFL injuries were higher than those in healthy controls (all p < 0.05). However, there were no significant differences in T2 values in subtalar and midtarsal joints between patients with isolated ATFL injuries and healthy controls (all p > 0.05). Moreover, T2 values of the medial talar subregions of the posterior subtalar joint in patients with combined CFL injuries showed negative correlations with the AOFAS scores (r = -0.687, p = 0.007; r = -0.609, p = 0.021, respectively). Conclusion CLAI with combined CFL injuries can lead to cartilage degeneration in subtalar and calcaneocuboid joints, while an isolated ATFL injury might not have a significant impact on the cartilage in these joints.

Objective:To investigate the effects of forced-air warming blankets combined with conventional warming strategies on the quality of postoperative recovery and cognitive recovery in elderly patients undergoing laparoscopic radical resection of colorectal cancer.Methods:This was a prospective, randomized, controlled trial.A total of 70 patients aged 65-75 years, who were classified as American Society of Anesthesiologists(ASA)grade-Ⅱ or Ⅲ, undergoing the laparoscopic radical resection of colorectal cancer under general anesthesia, were enrolled.Patients were randomly divided into two groups: the forced-air warming group(group FAW, n=35)and the conventional warming group(group CW, n=35). The inadvertent perioperative hypothermia(IPH), postoperative shivering, postoperative agitation, anesthesia recovery time and other postoperative complications were compared between the two groups.The post-operative quality of recovery scale(PQRS)was used to evaluate the quality of postoperative recovery and the recovery of cognitive function before and 1, 3, and 7 days after operation.Results:As compared with the group CW, the group FAW showed that the incidences of IPH, postoperative shivering and agitation were decreased(5.7% vs.22.8%, 2.8% vs.28.6%, 5.7% vs.31.4%, χ2=4.200, 10.057 and 7.652, P=0.042, 0.003 and 0.006), and the satisfaction degree of patients was increased at 48 hours after operation( P<0.01). The postoperative wake-up time was prolonged in the group CW as compared with the group FAW( P<0.01). Compared with the group CW, the proportion of patients with excellent overall recovery quality was increased in the group FAW 1 day after surgery( P<0.05). There was no significant difference in general recovery quality and cognitive recovery between the two groups at 3 and 7 days after operation. Conclusions:For elderly patients undergoing laparoscopic radical resection of colorectal cancer, the forced-air warming blanket combined with conventional warming strategies is more helpful to decrease the incidence of IPH, reduce postoperative shivering and improve the overall recovery quality at 1 day after operation, but no significant effect on postoperative recovery of cognitive function is found.

Objective: To determine the optimal dose of dexmedetomidine required to prevent nausea and vomiting when used for postoperative analgesia after gynecological laparoscopic surgery. Methods: A total of 135 patients, aged 18-60 yr, weighing 52-80 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective gynecological laparoscopic surgery, were divided into 3 groups (n=45 each) using a random number table method: control group (group C), dexmedetomidine 1 μg/kg group (group D₁) and dexmedetomidine 2 μg/kg group (group D₂). Immediately after anesthesia induction, dexmedetomidine 0.4 μg·kg^-1·h^-1 was injected intravenously until 30 min before the end of surgery in all the patients.When the patient was fully awake at the end of surgery, the tracheal tube was removed, and patients were sent to postanesthesia care unit and received patient-controlled intravenous analgesia (PCIA). The PCIA solution contained sufentanil 1.2 μg/kg and dezocine 20 mg in 100 ml of 0.9% normal saline.The PCIA pump was set up with a 0.5 ml bolus dose, a 15 min lockout interval and background infusion at a rate of 2 ml/h.Dexmedetomidine 1 and 2 μg/kg were added to PCIA solution in group D₁ and group D₂, respectively.The occurrence of nausea and vomiting was recorded in postanesthesia care unit stay period (P₁) and in 0-12 h (P₂), 12-24 h (P₃), 24-36 h (P₄) and 36-48 h (P₅) periods after patients returned to the ward.Ramsay sedation score was recorded at 12, 24, 36 and 48 h after patients returned to the ward.When visual analogue scale score >3, patients were told to press PCIA.Patients were followed up for 48 h after surgery, and patients′ satisfaction, pressing times of PCIA and occurrence of pruritus, respiratory depression, bradycardia and dizziness were recorded. Results: Compared with group C, the incidence of nausea was significantly decreased in P₂ period, and the pressing times of PCIA were reduced in P_{2, 3} period in D₁ and D₂ groups (P<0.05). There was no significant difference in Ramsay sedation score at each time point, patients′ satisfaction and incidence of bradycardia among the three groups (P>0.05). No patients developed pruritus, respiratory depression or dizziness in the three groups. Conclusion The optimal dose of dexmedetomidine required to prevent nausea and vomiting is 1 μg/kg when used for postoperative analgesia after gynecological laparoscopic surgery.

Objective To investigate the current status of job burnout among anesthetists in Ningxia and to analyze its related risk factors.Methods A total of 310 anesthetists from 30 public hospitals in Ningxia were conducted to collect data on the job burnout by Maslach Burnout InventoryHuman Services Survey (MBI-HSS).The factors associated with severe job burnout and its three domains (high emotional exhaustion,high depersonalization and low personal accomplishment) were included in the multinomial logistic regression analysis.Results The incidence of job burnout and its three domains (high emotional exhaustion,depersonalization and low personal accomplishment) were 18 (5.81％) cases,134 (43.22％) cases,35 (11.29％) cases and 128 (41.29％) cases,respectively.Multinomial logistic regression analysis results indicated that the risk degree associated with job burnout was master and higher degree (OR=4.695,95％CI 1.556-4.172).The risk facts associated with three components of job burnout were work time per week [40-60 h (OR=4.420,CI 2.504-7.802);≥60 h (OR =7.469,95％CI 1.758-31.733)] and tertiary hospital (OR =1.847,95％oCI 1.112-3.069);master and higher degree (OR=2.306,95％CI 1.032-5.155),working years [6-15 years (OR=0.358,95％CI 0.135-0.949)] and cases of anesthesia per year [≥390 cases (OR =3.352,95％CI 1.301-8.639)];secondary hospital (OR =1.717,95％CI 1.045-2.823).Conclusion This survey indicates that job burnout exists among anesthetists in Ningxia and is mainly displayed in emotional exhaustion and low personal accomplishment domains.Master and higher degree tend to occur serve job burnout.

Primary duodenal adenocarcinoma (PDA)is a rare but aggressive digestive tract malignancy,and its incidence is increasing in recent years. Early diagnosis of PDA is challenging due to nonspecific symptoms. Hence,it is often detected at an advanced stage. Treatment strategies tends to favor aggressive surgical resection. Adjuvant chemotherapy and radiation are important components of multi-modality treatment for patients with high risk of recurrence, and molecular targeted therapy is still in the exploratory stage. The best adjuvant therapy after operation is not yet clear. Early diagnosis and treatment is of great significance for prognosis. This article reviewed advances in epidemiology,risk factors,diagnosis,treatment and prognosis of PDA.

To investigate the relationship between single nucleotide polymorphisms (SNPs) of CACNA1C (SNPs rs58619945, rs7316246 and rs216008) and susceptibility of chronic spontaneous urticaria (CSU) as well as the curative effect of non-sedating antihistamine drugs.
 Methods: Peripheral blood were extracted from 191 CSU patients to collect DNA. Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI) changes were collected from these patients with different non-sedating antihistamine drugs. PubMed retrieval system was used to select the 3 SNPs (rs58619945, rs7316246 and rs216008) of CACNA1C. Susceptibility of CSU and curative effect of non-sedating antihistamine drugs (desloratadine, mizolastine, fisofenadine) in 189 CSU patients and 105 controls with different SNPs were compared with Chi-squared test. Data of 105 southern Chinese controls were extracted from the 1 000 genome database.
 Results: Frequency of rs58619945 G allele in the CSU patients was significantly higher than that in the controls [OR(95%CI)=0.660(0.470-0.925), P=0.016]. However, there was no significant differences in rs7316246 and rs216008 between the CSU patients and the controls. Meanwhile there was no significant difference in general curative effect of the 3 drugs in the 3 SNPs (rs58619945: OR=0.843, P=0.454; rs7316246: OR=2.103, P=0.102; rs216008: OR=0.237, P=0.363). There was significant difference in different alleles of rs216008 in the patients administered by desloratadine [OR(95%CI)=0.480(0.247-0.933), P=0.029]. No difference was shown in the 3 SNPs in patients administered by mizolastine.
 Conclusion: The rs58619945 A/G might be related to susceptibility of CSU, and the rs216008 mutation might affect drug response of desloratadine.
Calcium Channels, L-Type ; genetics ; Chronic Disease ; Genetic Predisposition to Disease ; Histamine H1 Antagonists, Non-Sedating ; therapeutic use ; Humans ; Loratadine ; analogs & derivatives ; therapeutic use ; Polymorphism, Single Nucleotide ; Prognosis ; Retrospective Studies ; Urticaria ; drug therapy ; genetics